The following references are referred to in the text by number:                1. U.S. Pat. No. 4,500,451 to Bohn, et al.        2. WO 99/38970 to Admon et al        3. Than, N. G., et al (1999) Placenta 20:703-710        4. U.S. Pat. No. 5,198,366 to Silberman        5. WO 00/58364 to Paltieli and Rabinovitch        6. U.S. Pat. No. 5,849,474 to Olson, et al.        7. U.S. Pat. No. 5,972,594 to Heine        
Each year, approximately one of every three pregnant women experiences a pregnancy-related complication, many being related to placental insufficiency. These figures are rising due to, among others, later pregnancies, inadequate nutrition, increased maternal smoking and the higher incidence of multi-fetal pregnancy. Pregnancy-related complications include spontaneous preterm delivery (SPTD), defined as delivery before the 37th gestation week, intrauterine growth retardation (IUGR), associated with the delivery of babies at the lower 3 percentile for age (severe IUGR) or the lower 10 percentile (mild IUGR), and preeclampsia (PE), defined as pregnancy-induced hypertension coupled to proteinuria. These complications negatively impact the outcome of affected pregnancies, at enormous cost both to the patients as well as to health-care systems.
Placental Protein 13 (PP13) is one of the 56 placental proteins identified to date. PP13 was previously isolated from human placental tissue (1, the contents of which are incorporated herein by reference). The protein was characterized by the following parameters: electrophoretic mobility, isoelectric point, sedimentation coefficient, molecular weight determined by ultracentrifugation, molecular weight determined by SDS-PAGE electrophoresis, extinction coefficient and carbohydrate content. The amino acid sequence of PP13 was determined, the full length cDNA was isolated, and the recombinant protein was expressed in various host cells. Sequence analysis revealed resemblence to erthrocyte lysophospholipase A (2). Computer assisted analysis of the deduced amino acid sequence showed that PP13 has the highest homology (56% identity) to the CLC protein, a unique dual-function lysophospholipase. Some authors hypothesize that PP13 is a member of the β-galactosidase binding S-type animal lectin (galectin) superfamily (3). The lysophospholipase activity of PP13 was observed using lysophosphatidylcholine as a substrate.
Utilizing immunoassays based on PP13 and its specific antibody, a test was developed for measuring maternal serum PP13 for predicting pregnancy complication such as severe IUGR, PE and SPTD during pregnancy (4, the contents of which are incorporated herein by reference). Both a radioimmunoassay (RIA) and an enzyme-linked immunosorbent assay (ELISA) were developed using labeled PP13 and anti PP13 polyclonal antiserum, respectively. However, experimental results were given only for the RIA, and not for the ELISA. No further properties of PP13 are disclosed in the Silberman patent. An immunoassay based on the recombinant PP13 is described in WO 99/38970. Subsequently, a more advanced method based on monoclonal antibodies to PP13 and recombinant PP13 was disclosed (5).
There have also been reports in the literature regarding the determination of other placental proteins and their relationship to pregnancy disorders.
A method of diagnosing preeclampsia in a pregnant female by detecting significantly elevated levels of a hemoglobin variant or its precursor, or a red blood cell glycolytic enzyme or its precursor has been disclosed (6).
A method of screening reproductive tract disease, inflammation and preeclampsia in humans by measuring the level of human neutrophil peptide defensins in a sample of bodily fluids has also been disclosed (7). Other measured parameters are beta HCG, PAPP-A, fetal fibronectin or estriol.